Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells: microarray and RNA interference studies.
17beta-estradiol (E(2)) binds estrogen receptor alpha (ESR1) in MCF-7 cells and increases cell proliferation and survival through induction or repression of multiple genes. ESR1 interactions with DNA-bound specificity protein (SP) transcription factors is a nonclassical genomic estrogenic pathway and the role of SP transcription factors in mediating hormone-dependent activation or repression of genes in MCF-7 cells was investigated by microarrays and RNA interference. MCF-7 cells were transfected with a nonspecific oligonucleotide or a cocktail of small inhibitory RNAs (iSP), which knockdown SP1, SP3, and SP4 proteins, and treated with dimethylsulfoxide or 10 nM E(2) for 6 h. E(2) induced 62 and repressed 134 genes and the induction or repression was reversed in approximately 62% of the genes in cells transfected with iSP (ESR1/SP dependent), whereas hormonal activation or repression of the remaining genes was unaffected by iSP (SP independent). Analysis of the ESR1/SP-dependent and SP-independent genes showed minimal overlap with respect to the GO terms (functional processes) in genes induced or repressed, suggesting that the different genomic pathways may contribute independently to the hormone-induced phenotype in MCF-7 cells.
Wu
Fei
F
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
Ivanov
Ivan
I
Xu
Rui
R
Safe
Stephen
S
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D051703:Sp Transcription Factors / Q000235:genetics / Q000378:metabolism*
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D051703:Sp Transcription Factors